PON1 polymorphisms and Wilms Tumor Gisele Moledo de Vasconcelos, - - PowerPoint PPT Presentation

PON1 polymorphisms and Wilms Tumor

Gisele Moledo de Vasconcelos, PhD Gonçalves BAA, Azevedo RM, Pombo‐de‐Oliveira MS, de Camargo B and the Brazilian Embryonic Tumor Group Pediatric Hematology‐Oncology Program Instituto Nacional de Câncer, Rio de Janeiro, Brazil

Exposures & Childhood Cancer 2012

Wilms tumor

Mature kidney Wilms tumor Fetal kidney 18 weeks

• Previous studies have shown an association of pesticides exposures

and Wilms Tumor risk.

Pesticides and Wilms Tumor

Pesticides and Wilms Tumor

Paraoxonase 1 (PON1)

• Hydrolyses active metabolites of organophosphorus pesticides.
• Levels of PON1 change according to age.
• And also due to polymorphims.

Polymorphisms in the gene PON1

PON1 Q192R – change activity PONL55M – change enzyme levels Children susceptibility to Wilms Tumor can be modified by PON1 genotypes: # their own genotype # and during pregnancy, in case of exposition, maternal genotype

Aims

• Identify the distribution of PON1 (Q192R and L55M) polymorphisms

and its relationship with Wilms tumor & embryonal neuroectodermal

• rigin tumors development in Brazilian children.
• Identify the frequencies of PON1

polymorphisms in mothers and the occurrence of embryonic tumors in their children.

Subjects and Methods

• Allelic discrimination (TaqMAN

probes)

• 47 Brazilian children with WT

and their mothers;

• 49 other embryonal tumors

(retinoblastoma, neuroblastoma and medulloblastoma) and their mothers;

• 190 health children and 117

mothers

Subjects and Methods

• Wilms Tumor patients: age ranged from 0 –

125 months.

• Other embryonal tumors: age range from 0 – 132 months.
• Children used as controls: age range from 0 – 60 months.
• There was no statistical difference according to gender in tumors

nor even in controls.

Results

• Mothers genotypes and children genotypes together:
• PON1

Q192R – QQ/QQ; QQ/QR; QR/QQ; QR/QR; RR/QR; RR/RR

• PON

L55M – LL/LL; LL/LM; LM/LL; LM/MM; MM/LM; MM/MM

• We observed no significant differences but N is too small.

Final Remark

• Despite the small series of cases , our preliminary results suggest

that PON1 Q192R polymorphism may be an important risk factor in the development of WT when children are exposed to pesticides.

Acknowledgements

• Ministério da Saúde
• Support Agencies
• Pediatric Hematology‐Oncology Program
• Brazilian Embryonic tumor group
• Dra. Maria do Socorro Pombo‐de‐Oliveira

& Dra. Beatriz de Camargo

• Rafaela Montalvão & Bruno A. Gonçalves

THANK YOU!